Some individuals who are asymptomatic for dementia while alive have substantial Alzheimer's disease (AD) neuropathology at autopsy. We investigated whether cognitive trajectories differ between clinically normal elderly individuals with and without AD neuropathology and how they compare with trajectories of clinically impaired individuals before dementia diagnosis. Eighty-one elderly participants in the Baltimore Longitudinal Study of Aging (BLSA) were followed prospectively with neurological and neuropsychological assessments before autopsy evaluation at death. Trajectories of cognitive change were estimated for a number of domains using cognitive data before a clinical diagnosis of dementia. Clinically normal elderly individuals with and without AD-type neuropathology have similar cognitive trajectories across different cognitive domains. In contrast, individuals with mild cognitive impairment/AD show steeper rates of longitudinal decline in several aspects of cognition compared with clinically normal elderly individuals regardless of whether the latter have AD neuropathology. Moreover, the cognitive differences between impaired and unimpaired groups can be detected years before a diagnosis of dementia. Clinically normal individuals with and without AD neuropathology do not differ in rates of cognitive decline across a number of cognitive domains. Understanding the factors that protect some individuals with AD pathology from cognitive impairment may contribute to the maintenance of cognitive health in the elderly.[unreadable] [unreadable] A longstanding riddle in the investigation of Alzheimers disease (AD) has been the finding of substantial numbers of A-beta plaques in the autopsy brains of some individuals with documented normal cognition. This study focuses on the morphometric changes of neurons in asymptomatic Alzheimer's disease (AD), a state characterized by the presence of AD lesions in subjects without cognitive impairment. In autopsy brains, we used stereological methods to compare the cell body and nuclear volumes of anterior cingulate gyrus (ACG) and CA1 hippocampal neurons in asymptomatic AD subjects (n=9), subjects with AD dementia (AD, n=8), mild cognitive impairment (MCI, n=9), and age-matched controls (controls, n=9). In ACG, we observed a significant decrease in the neuronal volume of MCI and AD compared to controls; by contrast, no atrophy was present in asymptomatic AD. Moreover, we found a significant increase in nuclear volume in asymptomatic AD compared to controls (P<0.001), MCI (P<0.01) and AD (P<0.001) brains. Similar results were found in the CA1 region of the hippocampus. This nuclear hypertrophy may represent an early neuronal reaction to Abeta or Tau, or a compensatory mechanism which forestalls the progression of AD and allows the brain to resist the development of dementia. Our results provide a novel finding of nuclear hypertrophy of ACG and CA1neurons in asymptomatic AD in comparison to age-matched controls, as well as MCI and AD. Moreover, the volume of the neuronal cell bodies in asymptomatic AD did not differ significantly from controls without significant AD pathology. By contrast, the volume of the neuronal cell bodies showed significant atrophy not only in AD but also in MCI.[unreadable] [unreadable] In HANDLS pilot study participants, we examined the association of total comorbid score and specific chronic conditions including cardiovascular diseases, musculoskeletal conditions, diabetes mellitus, stroke, hypertension, and cancer with several cognitive domains across four different age groups: young adults (ages 18-34), young middle-aged adults (ages 35-50), middle-aged adults (ages 51-64), and older adults (ages >64). Cognitive tests measuring global ability, executive function, memory function, and perceptual speed ability were administered to 384 African Americans. Total comorbid score was computed by summing up the number of chronic conditions. Results showed an inverse association between total comorbid scores and executive and memory functions in the total sample. With the exception of the youngest group, stroke was the only prominent predictor of poor performance for all age groups, but the impact was greater in the younger age groups compared with older adults. These results suggest that the impact of medical conditions on domain specific tasks may be modified by age.